The release of retrovirus particles from the infected cell is greatly stimulated by late domains present within the Gag precursor protein. Three distinct retroviral late-domain sequences have been identified: Pro-Thr/Ser-Ala-Pro (PTAP or PSAP), Pro-Pro-X-Tyr (PPXY, where X is any amino acid), and Tyr-Pro-Xn-Leu (YPXnL). We played a key early role in identifying the PTAP late domain of HIV-1, and, along with other labs, contributed to the discovery that late domains function by interacting with components of the endosomal sorting complex required for transport (ESCRT) machinery. We continue to be actively involved in elucidating the host cell machinery required for the release of HIV-1 and other lentiviruses (e.g., EIAV and FIV) and are in the process of identifying inhibitors of retrovirus budding. Much of our recent effort in this area is focused on the role of Alix in HIV-1 budding and cell-cell transfer. We have also initiated studies aimed at identifying and characterizing host cell factors that interfere with virus release. _____[Corresponds to Freed Project 2 in the October 2011 site visit report of the HIV DRP]